Premenstrual dysphoric disorder (PMDD) is a prevalent disorder in the spectrum of affective illness affecting woman, associated with significant morbidity. The neurobiology of this evolving, relatively understudied condition is not well understood. The aim of this study is to examine and characterize the systems-level neuropathophysiology of PMDD, taking into account menstrual cycle phase and menstrual cycle mood response variability of female subjects, in the context of a specific neurobiological model of fronto-limbic- striatal function. Specifically, we propose the use of functional magnetic resonance imaging (fMRI) methods with specific neuropsychological probes of emotional processing and behavioral control (functions of clinical relevance to the symptomatology of PMDD), and their interaction, in well-characterized patient samples, to test mechanistic hypotheses concerning fronto-limbic-striatal circuit dysfunction in PMDD, in comparison to asymptomatic female control subjects. We will examine the neural activity at two specified points in the menstrual cycle of each subject, once during the premenstrual phase (during the peak period of symptomatology in PMDD) and once during the postmenstrual phase. We hope to determine whether the provisional DSM-IV psychiatric diagnostic category of PMDD has an associated functional neuroanatomical profile in brain systems involved in the regulation of emotion and behavior. Such a neurobiological characterization of PMDD, in relation to asymptomatic female control subjects, can increase our understanding of the neurobiological spectrum of affective disorders. It is also of relevance given the increased incidence of mood and anxiety disorders in females, and will provide a necessary foundation for the development of more targeted, biologically based diagnostic and therapeutic strategies for PMDD.